Megaloblastic anaemia Flashcards
What is macrocytosis
An increase in the size of RBC . The size of RBC can be reflected by MCV and morphology reviewed on peripheral blood smear
What is megaloblastic anemia and what is the cause
- A group of disorders characterized by certain morphological changes in the developing RBC (asynchronous maturation ).
- Caused by a defect in DNA synthesis which affects all rapidly developing cells. Most commonly caused by Vit B12 def
There are 2 types of causes of macrocytic anemia ( result from abnormal erythropoiesis ) and other causes: Megaloblastic erythropoiesis & macronormoblastic erythropoiesis
- Causes megaloblastic erythropoiesis :
* Vit B12 def
* Folate def
* abnormal Vit B12 / folate metabolism
* antifolate drugs
* Defects of DNA synthesis inherited and acquired (zidovudine ) - Macronormoblastic erythropoiesis :
* alcohol
* liver disease
* Myelodysplastic syndrome
* Myxoedema
* aplastic anemia
* multiple myeloma - Other causes
* pregnancy
* neonates
* reticulocytes
* smoking
Discuss the biochemical basis of megaloblastic
*Deficiency of folate / Vit B12 is not converted into deoxythymidine monophosphate (dTMP ) resulting in a decreased supply of deoxythymidine triphosphate for DNA synthesis
Discuss folate absorption
*Absorbed in the upper small intestine ( in the duodenum and jejunum ) through the folate transporter proteins.
*Folate is easily destroyed by heat and the body stores last 4 months and can rapidly finish
*
Folate is converted into 5 methyl THF within the small intestine before they enter the plasma
*1/3 of folate is transported bound to the albumin and 2/3 is unbound
*daily requirement: 100 ug
Folate polyglutamate acts as co-enzyme involved in :
- Purine synthesis
- Pyrimidine synthesis
- Amino acid conversion to homocysteine to methionine
Causes of folate def
- Dietary ,alcoholism ,poverty , infants fed on goat milk
- malabsorption
- antifolate drugs (drugs wgich inhibit dihydrofolate reductase )
- pregnancy ,lactation ,prematurity
- haematological diseases ,malignancy ,inflammation and metabolic disease
- Excess urinary loss ,acute liver disease ,dialisus
Sources of Vit B12 (cobalamin )
*synthesized solely by a microorganism, liver, meat, fish, chicken, and dairy products.
- stores are enough for 3-4 years
- daily requirement: 1-5 ug
Which proteins bind to cobalamin
- Intrinsic factors: Gastric parietal cells :
- Transcobalamin: Synthesized by the liver, macrophages, and ilium
- Haptocorrins :
- R binder and TCI : transport in plasma to lievre
Cobalamin absorption
*Cobalamin enters the portal blood bound to 1 of two transporting proteins
: transcobalamin and haptocorrins
*Cobalamin - transcobalamin complex binds to a membrane receptor present on the surface of many cells
*transcobalamin is digested and cobalamin is released
Causes of severe cobalamin deficiency
- Vagens
- Malabsorption
- pernicious anaemia
- gastrectomy ( full/half)
- Congenital deficiency or functional abnormality
- ileal resection and Chron s disease
- fish tape
- Transcobalamin deficiency
Clinical findings common to all megaloblastic anemias
- Asymptomatic
- Anaemia: weakness, fatigue, palpitations, light-headed and shortness of breath
- Thrombocytopenia: may cause bruising
- Leucopenia: May predispose to infection
- Jaundice due to increased unconjugated hyperbilirubinaemia
- Angular stomatitis, anorexia
T/F: Cobalamin and folate def affects all dying cells
T, especially bone marrow followed by epithelial surfaces of the mouth, stomach, and genital tract.
The cells are large and many are dying
How to prevent neural tube defects in fetus
Supplementation with folic acid from conception for the first 12 weeks
Laboratory diagnosis of folate and cobalamin def
- RBC : D
- Hg : D
- HCT : D
- MCV : I
- MCHC : Normal
- RDW : I
- WBC : D
- PLt count : D
Pancytopenia: anaemia, neutropenia and thrombocytopenia
Biochemical evidence of ineffective erythropoiesis includes :
*Unconjugated hyperbilirubinemia
*decreased haptoglobin levels
*Increased urine urobilinogen
*Raised LDH
These finds are noted in certain hemolytic anemia
In megaloblastic, there is ineffective granulopoiesis and megakaryopoiesis resulting in pancytopenia
Diagnosing folate deficiency
*Serum levels :
> low
> affected by diet
>inadequate intake for one week can result in low levels
- RED CELL Folate :
- reflect body stores
*Megaloblastic anaemia resulting from folate def RBC folate is low and folate serum levels low
Diagnosis of cobalamin deficiency
*low levels with megaloblastic anemia, serum levels may be high and RBC folate levels low
*serum methylmalonic acid and homocysteine levels are increased
*
Treament for folate and cobalamin
*replacement therapy
> For patients with severe symptoms :
- Blood for both folate and cobalamin should be taken
- Bone marrow aspirate and trephine biopsy
- Replacement therapy: High doses of folate in presence of cobalamin def may aggregate neuropathy
> Avoid blood transfusion if possible :
- packed cells should be given slowly. Patients must be closely monitored for pulmonary edema and circulatory overload
- Platelets for patients with thrombocytopenia
Treatment for cobalamin deficiency
- Body stores should be replaced after 1000ug intramuscular injections of hydroxycobalamin given every 3-7 days
- 1000ug imi every 3 months
Treatment for folate deficiency
- given orally
- dose : 5-15 mg daily but exclude cobalamin def .
check cobalamin levels annually
5 mg daily for pregnant women
